Folic acid or combination of folic acid and vitamin B(12) prevents short-term arsenic trioxide-induced systemic and mitochondrial dysfunction and DNA damage

Environ Toxicol. 2009 Aug;24(4):377-87. doi: 10.1002/tox.20442.


The effect of folic acid and folic acid + vitamin B(12) supplementation upon short-term arsenic-induced systemic and pancreatic islet cell mitochondria oxidative stress was investigated in male rats. Arsenic trioxide was administered orally at a dose of 3 mg kg body weight(-1) day(-1) for 30 days, and folic acid and vitamin B(12) were administered at a dose of 36 and 0.63 microg kg body weight(-1) day(-1), respectively, for 30 days. Compared to control, arsenic-treated group showed a significant increase in the levels of systemic oxidative markers, malondialdehyde (MDA), nitric oxide (NO), and hydroxyl radical (OH(-)) formation, which were found decreased significantly after supplementation either with folic acid or a combination of folic acid + vitamin B(12). Similar supplementations were found effective against arsenic-induced oxidative marker changes (MDA, NO, and OH(-)) in pancreatic islet cell mitochondria. Also, low activities of antioxidant defense enzymes such as superoxide dismutase and catalase, and level of antioxidant glutathione, all could regain significantly on supplementations both against systemic and islet cell mitochondria oxidative stress. Results of agarose-gel electrophoresis of DNA from lymphocytes and islet cells of arsenic-exposed rats showed DNA smearing, which could be reduced with simultaneous administration either with folic acid or a combination of folic acid + vitamin B(12). Significantly, similar supplementations were found effective in increasing the urinary clearance of arsenic. Together, these results indicate that folic acid and vitamin B(12) may be effective to reduce the arsenic-induced damage at molecular target level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Arsenic Poisoning / prevention & control*
  • Arsenic Trioxide
  • Arsenicals / metabolism
  • Biomarkers / metabolism
  • Catalase / metabolism
  • Chemoprevention
  • DNA Damage / drug effects
  • Dehydroascorbic Acid / analogs & derivatives
  • Dehydroascorbic Acid / metabolism
  • Drug Therapy, Combination
  • Folic Acid / pharmacology*
  • Glutathione / metabolism
  • Islets of Langerhans / metabolism
  • Lymphocytes / metabolism
  • Male
  • Mitochondria / drug effects
  • Nitrites / metabolism
  • Oxidative Stress / drug effects
  • Oxides / metabolism
  • Oxides / toxicity*
  • Rats
  • Superoxide Dismutase / metabolism
  • Vitamin B 12 / pharmacology*


  • Antioxidants
  • Arsenicals
  • Biomarkers
  • Nitrites
  • Oxides
  • semidehydroascorbic acid
  • Folic Acid
  • Catalase
  • Superoxide Dismutase
  • Glutathione
  • Vitamin B 12
  • Arsenic Trioxide
  • Dehydroascorbic Acid